Portable infusion devices are known for automatic delivery of liquids, particularly insulin, these liquids being contained in replaceable injection ampules (European Patent Application No. 0,143,895, and the devices mentioned therein). Portable multidose injection devices, so-called "pens" (EP-A No. 0,058,536 and PCT Application WO No. 82/02,662) are furthermore known. However, these known devices, which are intended for multiple administration of the medicaments, are only suitable for homogeneous liquids, particularly solutions. In the case of disperse systems, such as medicament suspensions, the danger exists not only that crystal settling causes mechanical problems, but, above all, incorrect dosages are caused. Such incorrect dosages are particularly critical when the medicament is a highly-active medicament of narrow therapeutic range, such as, for example, insulin.
If, in the case of an insulin suspension, too few crystals are administered because the suspension has been inadequately shaken or has already settled again, hyperglycemia is to be expected, along with the known accompanying symptoms and with increased risk of later complications. If, in contrast, too much of the active ingredient is administered, hyperinsulinemia and hypoglycemia are to be feared, along with the accompanying serious symptoms, such as sweating, cramps and unconsciousness, up to death caused by hypoglycemic shock.
Medicament suspensions are usually filled into containers which also contain a gas space above the suspension. The suspension can then be homogenized by rolling, inverting or shaking this container. The presence of the gas bubble and its mobility is responsible for this. If, in contrast, the suspension is filled so that there is essentially no gas space, for example in cylindrical ampules from which multiple administrations are to take place, homogeneous mixing is normally not possible in a reasonable time. The physical basis of this phenomenon is that the density of crystals is generally very similar to the density of the medium.
In the case of dispensing devices in which multiple doses are to be administered from a stock, essentially gas bubble-free filling is necessary, however, since only then is reproduceable dose administraion ensured. "Essentially gas bubble-free" here is not intended to exclude a more or less large amount of gas being present initially, that is to say, for example, in the initial ampule, which is, however, removed in a known fashion before the first administration so that the liquid is then virtually free of gas bubbles. However, gas bubble-free crystal suspensions cannot be converted into the necessary homogeneous form by shaking in an acceptable period of time. It should particularly be taken into account here that such a homogenization must also be possible for old and handicapped patients.